Reaction #2161265

Reaction equation

[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid

HOBt

EDCI

NMM

1-piperidin-4-ylpyrrolidin-2-one hydrochloride

→

title compound

1(1-{[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)pyrrolidin-2-one

Solvents

DMA

Conditions

Workup

1. 1
   Otherthe mixture sonicated to a fine suspension
2. 2
   OtherThe volatiles were removed under high vacuum
3. 3
   Otherthe residue partitioned between EtOAc (70 mL) and water (25 mL)
4. 4
   OtherThe aqueous layer was removed
5. 5
   Washthe organics washed with NaHCO3 (30 mL), brine (30 mL)
6. 6
   Dryingdried over MgSO4
7. 7
   Filtrationfiltered

Procedure

To a solution of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (164 mg, 0.53 mmol) in DMA (3 mL) at room temperature was added HOBt (78 mg, 0.58 mmol), EDCI (111 mg, 0.58 mmol), NMM (0.20 mL, 1.84 mmol) and 1-piperidin-4-ylpyrrolidin-2-one hydrochloride (150 mg, 0.73 mmol) and the mixture sonicated to a fine suspension and stirred for 64 hours at room temperature. The volatiles were removed under high vacuum and the residue partitioned between EtOAc (70 mL) and water (25 mL). The aqueous layer was removed and the organics washed with NaHCO3 (30 mL), brine (30 mL), dried over MgSO4, filtered and stripped to yield the title compound as an off-white solid, 123 mg, 51%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.51-8.54 (2 H, m), 7.64-7.69 (2 H, m), 7.25-7.35 (2 H, m), 7.11-7.21 (2 H, m), 6.53 (1 H, s), 5.11-5.28 (2 H, m), 4.37 (1 H, d, J=13.14 Hz), 3.90-4.05 (4 H, m), 3.23-3.31 (2 H, m), 3.08-3.20 (1 H, m), 2.57-2.70 (1 H, m), 2.22 (2 H, t, J=8.08 Hz), 1.84-1.95 (2 H, m), 1.40-1.73 (4 H, m); m/z (APCI+) for C26H28N5O2F 462.2 (M+H)+.

Source